Protein Section, Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Computational Biology Branch, National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, 20892, USA.
Nat Commun. 2018 Dec 7;9(1):5240. doi: 10.1038/s41467-018-07687-9.
The dynamic nature of the chromatin epigenetic landscape plays a key role in the establishment and maintenance of cell identity, yet the factors that affect the dynamics of the epigenome are not fully known. Here we find that the ubiquitous nucleosome binding proteins HMGN1 and HMGN2 preferentially colocalize with epigenetic marks of active chromatin, and with cell-type specific enhancers. Loss of HMGNs enhances the rate of OSKM induced reprogramming of mouse embryonic fibroblasts (MEFs) into induced pluripotent stem cells (iPSCs), and the ASCL1 induced conversion of fibroblast into neurons. During transcription factor induced reprogramming to pluripotency, loss of HMGNs accelerates the erasure of the MEF-specific epigenetic landscape and the establishment of an iPSCs-specific chromatin landscape, without affecting the pluripotency potential and the differentiation potential of the reprogrammed cells. Thus, HMGN proteins modulate the plasticity of the chromatin epigenetic landscape thereby stabilizing, rather than determining cell identity.
染色质表观遗传景观的动态特性在细胞身份的建立和维持中起着关键作用，但影响表观基因组动态的因素尚不完全清楚。在这里，我们发现普遍存在的核小体结合蛋白 HMGN1 和 HMGN2 优先与活跃染色质的表观遗传标记以及细胞类型特异性增强子共定位。HMGNs 的缺失增强了 OSKM 诱导的将小鼠胚胎成纤维细胞（MEFs）重编程为诱导多能干细胞（iPSCs）的速度，以及 ASCL1 诱导的成纤维细胞向神经元的转化。在转录因子诱导的重编程为多能性过程中，HMGNs 的缺失加速了 MEF 特异性表观遗传景观的擦除和 iPSCs 特异性染色质景观的建立，而不影响重编程细胞的多能性潜力和分化潜力。因此，HMGN 蛋白调节染色质表观遗传景观的可塑性，从而稳定细胞身份，而不是决定细胞身份。
